Stewardship / Resistance Scan for Jul 18, 2017

News brief

More antibiotic prescriptions in UK coming from non-medical prescribers

A retrospective analysis of antibiotic prescriptions in England published yesterday in the Journal of Antimicrobial Chemotherapy found that nearly 8% of all antibiotics dispensed in primary care are prescribed by non-medical prescribers (NMPs), mostly nurses.

In the United Kingdom, NMPs—appropriately qualified non-medical healthcare professionals such as nurses, pharmacists, and allied health professionals—have the authority to independently prescribe medicine within their area of competence. They work in a variety of settings and provide a broad range of healthcare services, and their numbers are rising. To date, however, there have been no available data on the pattern of antibiotic prescribing by NPMs in England.

Using data from the National Health Service (NHS), researchers found that from July 2011 through December 2015, the number of NMPs rose by 38.5% (from 21,545 to 29,836). Of these prescribers, 89.8% were nurses, 9.9% were pharmacists, and 3.3% were allied health professionals. While the rate of all antibiotics dispensed per NMP decreased over the study period, the volume increased, with the percentage of all primary care antibiotics dispensed that were prescribed by NMPs rising from 5.6% to 7.6%, a 37.1% increase.

The vast majority of these dispensed NMP prescriptions for antibiotics were written by nurses, but the percent declined over time, from 28.79 per nurse prescriber at the beginning of 2011 to 26.22 per nurse prescriber by the end of 2015. Dispensed pharmacists' prescriptions for antibiotics, in contrast, increased from 0.83 per prescriber in January 2011 to 4.08 per prescriber in October 2015.

Penicillins were the most commonly prescribed antibiotics, followed by sulphanomides and trimethoprim, macrolides, tetracyclines, and nitrofurantoin. The data did not allow researchers to make any judgment on the appropriateness of these prescriptions

The authors conclude that with the number of NMPs in England set to rise in coming years, this group should be involved in antimicrobial stewardship efforts.
Jul 17 J Antimicrob Chemother abstract


Small study finds FMT reduces frequency of recurrent UTIs

Fecal microbiota transplantation (FMT) for treatment of recurrent Clostridium difficile infection (CDI) significantly decreased recurrent urinary tract infection (UTI) frequency and improved the antibiotic susceptibility profile of UTI-causing organisms in a small study today in Clinical Infectious Diseases.

In the study, Mayo Clinic investigators retrospectively identified eight patients who had undergone FMT for recurrent CDI (three or more episodes) and had three or more UTIs in the year preceding FMT. These patients were with to a control group of eight patients who had recurrent CDI managed with antibiotics and had three or more UTIs in the year prior to the third CDI episode.

Based on a previous study that found FMT for recurrent CDI eradicated vancomycin-resistant Enterococci (VRE) colonization in 73% of VRE-positive patients, the researchers hypothesized that FMT might also reduce the frequency of recurrent UTIs from antibiotic-resistant organisms by decolonizing multidrug-resistant organisms (MDROs) from the gut.

The results showed a significant decrease in the frequency of UTIs among the case-patients, from a median of four episodes in the year before to one episode in the year after FMT (P = 0.01). Positive urine samples cultured in the year before and after FMT showed a reduction in the most common organisms cultured, with Escherichia coli–positive samples dropping from 15 before FMT to 4 after, and Klebsiella pneumoniae-positive samples dropping from 9 to 1. In addition, susceptibility testing conducted after FMT showed a reduction in the number of E coli and K pneumoniae isolates that were resistant to ampicillin, ciprofloxacin, trimethoprim-sulfamethoxazole, and nitrofurantoin.

By comparison, the patients managed with antibiotics saw no difference in the frequency of UTIs in the year before and after the third CDI episode (a median of four UTI episodes), and no changes in antimicrobial resistance patterns in E coli and K pneumoniae isolates before and after antibiotic treatment.

"Although our findings are limited by a small sample size and lack of microbiome profiling, we demonstrate that FMT may decrease the frequency of MDRO UTIs possibly by gut decolonization through reestablishment of colonization resistance," the authors write. "This effect may lead to decreased antibiotic use, morbidity, and cost."
Jul 18 Clin Infect Dis abstract

News Scan for Jul 18, 2017

News brief

MERS diagnosed later in older patients

A study yesterday in the International Journal of Infectious Diseases that measured the time between symptom onset and diagnosis in 537 patients with MERS-CoV in Saudi Arabia found that patients were diagnosed 0 to 36 days after symptoms appeared, with a median of 4 days.

However, patients who are more likely to suffer severe outcomes from MERS-CoV (Middle East respiratory syndrome coronavirus), including the elderly and those with preexisting illnesses, had longer delays in diagnosis than younger and healthier people.

According to the study, the rate of delayed diagnosis was 42% higher in patients older than 65 compared  with patients younger than 30. The authors suggest this may be why older patients are more likely to die from MERS-CoV than younger patients.

Patients with severe symptoms were also diagnosed more than 2 days later than patients who were in stable condition.
Jul 17 Int J Infect Dis study


Review of cholera vaccine studies affirms solid protection for at least 3 years

A meta-analysis of the most recent efficacy estimates for killed oral cholera vaccines suggests that they provide medium to high levels of protection for at least 3 years with the two-dose schedule and can provide similar short-term protection with one dose. A team based at the Johns Hopkins Bloomberg School of Public Health reported its findings yesterday in The Lancet Infectious Diseases.

For their review, the scientists included data from seven randomized, controlled efficacy trials, most with a placebo group, and six observational studies involving lab-confirmed cholera. All of the studies were published since 2010 to provide an updated and more complete picture of the vaccine's protection.

Taken together, the studies showed an average two-dose efficacy of 58% (95% confidence interval [CI], 42% to 69%) and effectiveness of 76% (95% CI, 62% to 85%). Efficacy for children younger than 5 years old was lower than their older counterparts, 30% and 64%, respectively.

The two-dose efficacy estimates were similar for the first 2 years after vaccination, with the level declining to 39% in the third year and 26% in the fourth year. Short-term effectiveness was similar between one- and two-dose regimens.

The researchers said the findings suggest that the one-dose protection findings lend support to using one dose as a practical option for reducing short-term risk in outbreak settings.

In a related commentary, two experts from the Indian Council of Medical Research wrote that the new estimates affirm earlier findings and that the low efficacy in the youngest children continues to influence vaccine policy discussions in endemic countries. They said a better understanding of the reasons for the poor immune response in the age-group are needed, as is the extent of herd protection offered by the vaccines, especially as it affects children.

Cheap, effective oral cholera vaccines offer a viable option for helping to keep cholera at bay, given that water and sanitation improvements can take a long time to implement and the fact that the Vibrio bacteria that cause the disease are known to persist in the environment.
Jul 17 Lancet Infect Dis abstract
Jul 17 Lancet Infect Dis commentary


Study finds limited impact of flu vaccine on flulike illness in seniors

Flu vaccination in older adults reduces the number of infections from flu, but not the number influenza-like illnesses (ILIs), suggesting that other pathogens fill the gap, researchers from the Netherlands reported last week in the Journal of Infectious Diseases.

In a prospective, test-negative, observational study designed to measure the contributions of flu and other respiratory pathogens, the team followed adults age 60 and older over during the 2011-12 and 2012-13 flu seasons, both of which had H3N2 as the dominant strain. They collected nose and throat swabs from sick people and controls to identify viruses and bacteria. They also recorded participants' flu vaccination status.

Influenza was responsible for 18.9% of the ILIs the first season and for 34.2% the following season. Pathogens were detected in 80% of ILI episodes, with influenza, coronaviruses, rhinoviruses, human metapneumovirus, respiratory syncytial virus, parainfluenza virus, and Haemophilus influenzae most common.

Flu vaccination cut the level of infections specifically from flu by 73% (95% CI, 26% to 90%) the first season and 51% (95% CI, 7% to 74%) the second season. The incidence of ILI, however, was similar for both the vaccinated and unvaccinated groups: 7.6% and 4.2%, respectively, the first season and 10.8% and 11.4%, respectively, the second season.

The authors suggested that because other pathogens seem to take up the slack carved out by flu vaccination, there may be a pool of people who are highly susceptible to respiratory infections.

In a related commentary, two Canadian experts wrote that test-negative study designs, which help to ease the healthy vaccinee bias, are helping to tease out the benefits and gaps in flu vaccine protection in older people. They noted that the researchers acknowledged that their study may overestimate the benefit of vaccination, since it involved a relatively healthy population. The commenters noted the importance of factoring in frailty measures and focusing on H3N2 seasons to assess the effectiveness of flu vaccines in older adults.
Jul 13 J Infect Dis abstract
Jul 13 J Infect Dis commentary


New highly sensitive, specific Zika test highlighted

An international research team yesterday described a new diagnostic test for Zika virus that can reliably distinguish it from similar viruses, offering a simple, cost-effective tool for surveillance and clinical management. The group, based at the University of California-Berkeley, reported its findings in Proceedings of the National Academy of Sciences (PNAS).

The antibody test is based on a nonstructural protein 1 (NS1) human monoclonal antibody and was developed by scientists at UC-Berkeley and Humabs BioMed, a private biotechnology company. The work was partly supported by the National Institutes of Health.

The assay was developed from 14 years' worth of patient samples from a collection in Nicaraguan children who had well-documented infections. The collection included longitudinal samples from Zika patients, including those with or without earlier dengue infection and those infected with more than one dengue subtype.

To gauge the sensitivity and specificity of the new assay, the investigators tested a large number of samples from travelers and people with high exposure to Zika and other flaviviruses in five countries. Results showed that the assay was highly sensitive (91.8%) and highly specific (95.9%) for Zika virus.

The assay is based on the ELISA platform, which is widely available throughout the world, and the authors estimated that the cost for reagents and materials is about 25 cents. They also note that the test is a single assay, requiring only one dilution per sample.

Eva Harris, PhD, study coauthor and professor of infectious diseases at UC-Berkeley, said in a statement from the university, "The whole world has been in urgent need of a serological method to distinguish dengue virus from Zika virus infections, and this the first to have such high sensitivity and specificity in dengue-endemic regions."
Jul 17 PNAS abstract
Jul 18 UC-Berkeley press release

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